The cause of syphilis, Treponema pallidum, has never been cultivated in vitro. The inability to grow this organism in large numbers has prevented investigations leading to the development of a useful vaccine, studies on the mechanism of disease production, and the solution of complex immunologic problems associated with this disease. We are trying to cultivate this treponeme in the laboratory by a) obtaining information on substrate oxidation and incorporation, and extending previous findings from this laboratory on oxygen requirements of tissue grown treponemes, b) identifying intermediate or end-products of substrate oxidation, c) determining the mechanism for terminal electron transport, d) investigating the possibility for coupled oxidative phosphorylation, and e) applying this information to attempts to cultivate this organism in vitro.